This invention relates to materials and methods for the construction of recombinant viral, particularly adenoviral, delivery systems that provide lens epithelial cell type specific regulation of expression of proteins which inhibit cellular proliferation. This invention also relates to the use of these recombinant viral delivery systems for inhibiting or preventing the formation of secondary cataracts following surgical intervention on the eye.
Cataract operations are the second most frequent operation in the western world. The cataract is an affliction characterized by an opacification of the crystalline lens of the eye which reduces the visual acuity of the patient. The surgical technique currently utilized for removing cataracts consists of removing the crystalline with a small aspirator. Access to the interior of the crystalline capsule is achieved by a circular opening at the anterior face of the lens capsule. This permits the surgeon to insert a new lens, which will restore the eye's ability to focus incoming light on the surface of the retina.
Secondary cataracts constitute the most frequent complication following this operation, occurring in up to 50% of adult eyes and even more frequently following surgery of children with congenital cataracts (Nischi et al., 1986). (Surgical interventions on the eyes of rabbits also result in secondary cataract formation (100%) in the weeks following the operation (Blomstedt. et al., 1987)). Human secondary cataracts are characterized by a secondary opacification of the posterior capsule appearing in the months following surgery. They are the consequence of the stimulated proliferation at the level of the germinative epithelium of the lens, which are the only cells with division potential in the mature eye. Laser treatment, which is the accepted means of treating secondary cataracts, unfortunately risks additional complications, the most notable of which is detachment of the retina (Salvenson et al., 1991).